Alvac canarypox virus recombinants comprising heterlogous inserts

Abstract

What is described is a modified vector, such as a recombinant poxvirus, particularly recombinant vaccinia virus, having enhanced safety. The modified recombinant virus has nonessential virus-encoded genetic functions inactivated therein so that virus has attenuated virulence. In one embodiment, the genetic functions are inactivated by deleting an open reading frame encoding a virulence factor. In another embodiment, the genetic functions are inactivated by insertional inactivation of an open reading frame encoding a virulence factor. What is also described is a vaccine containing the modified recombinant virus having nonessential virus-encoded genetic functions inactivated therein so that the vaccine has an increased level of safety compared to known recombinant virus vaccines.\!

What is claimed is: 
     
       1. An attenuated virus having all the identifying characteristics of: an ALVAC canarypox virus.   
     
     
       2. A virus which is ALVAC. 
     
     
       3. A vector which comprises the virus of claim 1. 
     
     
       4. A vector which comprises the virus of claim 2. 
     
     
       5. A virus as claimed in claim 2 further comprising exogenous DNA from a non-poxvirus source in a nonessential region of the virus genome. 
     
     
       6. A virus as claimed in claim 5 wherein the exogenous DNA is selected from the group consisting of rabies virus, Hepatitis B virus, Japanese encephalitis virus, yellow fever virus, Dengue virus, measles virus, pseudorabies virus, Epstein-Barr virus, herpes simplex virus, human immunodeficiency virus, simian immunodeficiency virus, equine herpes virus, bovine herpes virus, bovine viral diarrhea virus, human cytomegalovirus, canine parvovirus, equine influenza virus, feline leukemia virus, feline herpes virus, Hantaan virus, C. tetani, avian influenza virus, mumps virus and Newcastle Disease virus. 
     
     
       7. A virus as claimed in claim 6 wherein the virus is a canarypox virus, the non-poxvirus source is rabies virus, and the canarypox virus is vCP65 or vCP136. 
     
     
       8. A virus as claimed in claim 6 wherein the virus is a canarypox virus, the non-poxvirus source is human immunodeficiency virus and the canarypox virus is vCP95, vCP112, vCP60, vCP61, vCP125, vCP124, vCP126, vCP144, vCP120, vCP138, vCP117, vCP130, vCP152, vCP155, vCP156, vCP146, vCP148, vCP154, vCP168 or vCP153. 
     
     
       9. A virus as claimed in claim 6 wherein the virus is a canarypox virus, the non-poxvirus source is equine herpes virus and the canarypox virus is vCP132. 
     
     
       10. A virus as claimed in claim 6 wherein the virus is a canarypox virus, the non-poxvirus source is human cytomegalovirus and the canarypox virus is vCP139. 
     
     
       11. A virus as claimed in claim 6 wherein the virus is a canarypox virus, the non-poxvirus source is canine parvovirus and the canarypox virus is vCP123 or vCP136. 
     
     
       12. A virus as claimed in claim 6 wherein the virus is a canarypox virus, the non-poxvirus source is Epstein-Barr virus and the canarypox virus is vCP167. 
     
     
       13. A virus as claimed in claim 6 wherein the virus is a canarypox virus, the non-poxvirus source is equine influenza virus and the canarypox virus is vCP128 or vCP159. 
     
     
       14. A virus as claimed in claim 6 wherein the virus is a canarypox virus, the non-poxvirus source is feline leukemia virus and the canarypox virus is vCP177, vCP83, vCP35, vCP37, vCP87, vCP93 or vCP97. 
     
     
       15. A virus as claimed in claim 6 wherein the virus is a canarypox virus, the non-poxvirus source is feline herpes virus and the canarypox virus is vCP162. 
     
     
       16. A virus as claimed in claim 6 wherein the virus is a canarypox virus, the non-poxvirus source is Hantaan virus and the canarypox virus is vCP114 or vCP119. 
     
     
       17. A virus as claimed in claim 6 wherein the virus is a canarypox virus, the non-poxvirus source is Hepatitis B and the canarypox virus is vCP169 or vCP157. 
     
     
       18. A virus as claimed in claim 6 wherein the virus is a canarypox virus, the non-poxvirus source is C. tetani and the canarypox virus is vCP161. 
     
     
       19. A virus as claimed in claim 6 wherein the virus is a canarypox virus, the non-poxvirus source is mumps virus and the canarypox virus is vCP171. 
     
     
       20. A virus as claimed in claim 6 wherein the virus is a canarypox virus, the non-poxvirus source is Japanese encephalitis virus and the canarypox virus is vCP107 or vCP140. 
     
     
       21. A virus as claimed in claim 6 wherein the virus is a canarypox virus, the non-poxvirus source is simian immunodeficiency virus, and the canarypox virus is vCP172. 
     
     
       22. A virus as claimed in claim 6 which is a rabies virus recombinant canarypox virus which is vCP65. 
     
     
       23. A virus as claimed in claim 6 which is a human immunodeficiency virus recombinant canarypox virus which is vCP95, vCP112, vCP60 or vCP61. 
     
     
       24. A virus as claimed in claim 1 further comprising exogenous DNA from a non-poxvirus source in a non-essential region of the virus genome. 
     
     
       25. An immunological composition for inducing an immunological response in a host animal inoculated with said composition, said composition comprising the virus of any one of claims 1, 2 or 5 to 24, or, a vector as claimed in claim 3 or 4, and a carrier. 
     
     
       26. The immunological composition of claim 25 which is a vaccine. 
     
     
       27. A method of expressing a gene product in a cell cultured in vitro comprising introducing into the cell a virus as claimed in any one of claims 1, 2 or 5 to 24, or, a vector, transforming cell with the expression vector, cultivating the transformed cell under conditions which allow expression of the recombinant poxvirus, and further purifying the protein as claimed in claim 3 or 4.